Inside this issueCover storiesFollowing in his father’s footsteps$3 billion Yale campaign will benefit science and medicineNew genes found in Crohn’s disease, serious eye ailmentPartnershipsState makes first stem-cell grants to YaleGrants & contractsPeopleLifelines: Joseph SchlessingerPediatric researcher is new ambassador for global healthBiologist cited for structural insights into action of antibioticsExpert on blood pressure is honoredEducation innovator wins award for work on transforming schoolsOut & aboutAwards & honorsHealthA robot arrives in the operating roomScienceA crystal-clear look at a puzzling proteinMagnetic resonance system will open new scientific vistasAdvances: In bacteria vs. worm, children are winners | Ruling fate of cellular blank slate | How the stressed become the depressed | The immune system in a sticky situation  
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AdvancesHealth and science news from YaleIn bacteria vs. worm, children are winners
If the bacterium Bacillus thuringiensis (Bt) did battle against the parasitic hookworm Ancylostoma ceylanicum, who would prevail? According to new research, the biggest victors may be the nearly 1 billion people infected by hookworms worldwide—especially children, who risk anemia, malnutrition and growth delay. Bt-produced substances known as crystal proteins are commonly used on crops to control insects and worms. Michael Cappello, M.D., professor of pediatrics, microbial pathogenesis and public health, and colleagues at the University of California, San Diego, found that a Bt crystal protein known as Cry5B might also be an effective treatment for parasitic worm infections. In the October 10 issue of the Proceedings of the National Academy of Sciences, Cappello and colleagues report that Cry5B inhibits hookworm growth in laboratory dishes and in infected hamsters. In the hamsters, Cry5B was as potent as a conventional anti-parasite medication in reversing weight loss and anemia, and no toxic effects were evident. Ruling the fate of a cellular blank slateStem cells make identical copies of themselves and can differentiate into many of the myriad cell types that form the body’s tissues and organs. To maximize these cells’ therapeutic versatility, they must be maintained in an undifferentiated state. Some researchers have suggested that oxygen levels are low within the stem cell niche—the microenvironment within tissues that determines whether stem cells regenerate or differentiate. Seeking a method to preserve stem cells in their blank slate form, Zhong Yun, Ph.D., assistant professor of therapeutic radiology, and colleagues took a cue from nature, mimicking those low-oxygen conditions for cells in the lab. As reported in the October 13 issue of The Journal of Biological Chemistry, under these conditions stem cell-like fat precursor cells remained in an undifferentiated state. And when the team upped the oxygen level, the precursor cells could again be converted into fat cells. “Once we know how the microenvironment regulates the functions of stem and progenitor cells,” says Yun, “we can potentially protect them from premature differentiation or find ways to mobilize these cells for tissue repair and regeneration.” How the stressed become depressed
Some individuals persevere in hardship; others crumple like paper dolls. Mental fortitude in the face of stress has been linked to variations in a gene that regulates the neurotransmitter serotonin: individuals with a short version of the gene have a greater propensity to fall into depression under stress, while those with the longer version are more resilient. To gain a glimpse of how these genetic differences might interact with stress to produce depression, R. Todd Constable, Ph.D., professor of diagnostic radiology and biomedical engineering, and colleagues in New York and Germany used brain imaging while individuals carrying short or long forms of the gene looked at images of faces. Other work had suggested that short-gene carriers who had experienced life stress would show an elevated response to sad or fearful faces in brain areas involved in depression and coping. But in the October 24 issue of Proceedings of the National Academy of Sciences, Constable and colleagues reported less activation in short-gene carriers under these conditions and greater activation at rest. This pattern may reflect “a chronic state of vigilance, threat, or rumination” in short-gene carriers that makes them more vulnerable to depression under stress. The immune system in a sticky situationNeutrophils, critical cells of the early immune response, travel quickly through the bloodstream to sites of infection to engulf and kill bacteria. If genetic defects slow down this neutrophil migration, more severe infections may result. School of Medicine researchers have now identified a key gene that regulates neutrophil movement through the body, which may clarify why some individuals are more susceptible to infection and inflammation. A team led by Richard A. Flavell, Ph.D., Sterling Professor and chair of Immunobiology and Howard Hughes investigator, reports in the October 6 issue of Science that mice lacking the gene Myo1f have neutrophils that adhere more readily to their surroundings and are therefore markedly slower in reaching sites of infection. Myo1f, not previously known to play a role in immunity, limits the number of proteins known as integrins on the cell surface. In the gene’s absence, more integrins are released, making neutrophils more sluggish. “Without Myo1f, immune cells get too sticky and cannot move fast,” says first author Sang-won V. Kim, Ph.D., now at Memorial Sloan-Kettering Cancer Center. “So the host becomes vulnerable to acute infection.”  |
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